Acute kidney injury

Etiology

---

Intrinsic acute kidney injury

Intrinsic causes include any condition that leads to severe direct kidney damage (∼ 35% of cases of AKI).

Info

ATI is an umbrella term indicating a sudden decrease in kidney function. GN, ATN, and ATIN are all causes of ATI.

• Acute tubular necrosis (causes ∼ 85% of intrinsic AKIs)
  • Ischemia: e.g., due to prolonged hypotension
  • Nephrotoxic drugs: e.g., radiographic contrast agents, aminoglycosides, cisplatin, methotrexate, ethylene glycol, amphotericin B
  • Endogenous toxins: e.g., hemoglobin in intravascular hemolysis, myoglobin in rhabdomyolysis, uric acid in TLS, Bence-Jones protein light chains in multiple myeloma
• Acute interstitial nephritis
  • Medication: e.g., antibiotics , phenytoin, interferon, PPIs, NSAIDs, cyclosporine
  • Infection
    • Bacterial: e.g., Legionella spp., Streptococcus spp.
    • Fungi: Candida, Histoplasma
    • Viral: e.g., hepatitis C virus, cytomegalovirus, HIV
  • Infiltrative diseases: e.g., sarcoidosis, amyloidosis
• Vascular diseases
  • Hemolytic uremic syndrome (HUS)
  • Thrombotic thrombocytopenic purpura (TTP)
  • Hypertensive emergency
  • Vasculitis, scleroderma renal crisis
  • Renal vein thromboses, renal atheroemboli, renal infarction
• Glomerulonephritis:e.g., rapidly progressive glomerulonephritis

Pathophysiology

---

Prerenal

• Decreased blood supply to kidneys (due to hypovolemia, hypotension, or renal vasoconstriction) → failure of renal vascular autoregulation to maintain renal perfusion → decreased GFR → activation of renin-angiotensin system → increased aldosterone release → increased reabsorption of Na⁺, H₂O → increased Urine osmolality → secretion of antidiuretic hormone → increased reabsorption of H₂O and urea
• Creatinine is still secreted in the proximal tubules, so the blood BUN:creatinine ratio increases.

Intrinsic

• Damage to a vascular or tubular component of the nephron → necrosis or apoptosis of tubular cells → decreased reabsorption capacity of electrolytes (e.g., Na⁺), water, and/or urea (depending on the location of injury along the tubular system) → increased Na⁺ and H₂O in the urine → decreased Urine osmolality

Postrenal

Four phases of AKI

1. Initiating event (kidney injury) (Duration: Hours to days)
   • Symptoms of the underlying illness causing AKI may be present.
2. Oliguric or anuric phase (maintenance phase) (Duration: 1-3 weeks)
   • Progressive deterioration of kidney function
     • Reduced urine production (oliguria), < 50 ml/24 hrs = anuria
     • Increased retention of urea and creatinine (azotemia)
   • Complications: fluid retention (pulmonary edema), hyperkalemia, metabolic acidosis, uremia, lethargy, asterixis
3. Polyuric/diuretic phase (Duration: ~ 2 weeks)
   • Glomerular filtration returns to normal, which increases urine production (polyuria), while tubular reabsorption remains disturbed.
   • Complications: loss of electrolytes and water (dehydration, hyponatremia, and hypokalemia)
4. Recovery phase (Duration: Months to years)
   • Kidney function and urine production normalize.

Clinical features

---

Subtypes and variants

---

Acute tubular necrosis

• Epidemiology: causes ∼ 85% of intrinsic AKIs
• Location
  • The straight segment of the proximal tubule and the straight segment of the distal tubule (i.e., the thick ascending limb) are particularly susceptible to ischemic damage.
    • Blood flow in the renal medulla is relatively low compared to that in the renal cortex.
      • Facilitates the development of an osmolality gradient that allows for effective urine concentration
      • Causes medullary vulnerability to hypoxia when renal blood flow is decreased (renal ischemia)
  • The convoluted segment of the proximal tubule is particularly susceptible to damage from toxins (but can also damage from ischemia).
    • First encounters toxins
  • Descending and ascending limbs are not, as their function is primarily passive.
• Etiology
  • Ischemic: Injury occurs secondary to decreased renal blood flow.
    • Severe hypotension, especially in the context of shock: hypovolemic (e.g., hemorrhage, severe dehydration), septic, cardiogenic (e.g., heart failure), or neurogenic shock
    • Cholesterol embolism (atheroemboli)
  • Toxic: Injury occurs directly due to nephrotoxic substances.
    • Contrast-induced nephropathy
    • Medication: aminoglycosides, cisplatin, amphotericin, lead, ethylene glycol
    • Pigment nephropathy
      • Myoglobinuria due to rhabdomyolysis (crush syndrome)
      • Hemoglobinuria associated with hemolysis
• Pathophysiology: necrotic proximal tubular cells fall into the tubular lumen → debris obstructs tubules → decreased GFR → sequence of pathophysiological events similar to prerenal failure
• Diagnostic

Acute tubular necrosis vs Renal papillary necrosis

• ATN: Oliguria
  • Causes: ischemic or toxic
• RPN: Flank pain, hematuria
  • Causes: sickle cell disease, NSAIDs

Diagnostics

---

Urine sediment

• Prerenal: hyaline casts due to concentrated urine in the setting of low renal perfusion
• Intrinsic: renal tubular epithelial cells or granular, muddy brown, or pigmented casts
• Postrenal: none

Feature	Acute Tubular Necrosis (ATN)	Acute Tubulointerstitial Nephritis (AIN)	Renal Papillary Necrosis (RPN)
Core Problem	Tubular cell death (ischemia/toxins)	Allergic/inflammatory reaction in interstitium & tubules	Necrosis of renal papillae
Key Causes	Shock, Sepsis, Aminoglycosides, Contrast, Myoglobin	Drugs (NSAIDs, Penicillins, PPIs, Sulfa), Infections	NSAIDs, Sickle Cell, Diabetes, Pyelonephritis, Obstruction
Classic Presentation	AKI after hypotension or nephrotoxin exposure	Fever, Rash, Arthralgia (triad often absent), AKI after new drug	Hematuria, Flank Pain (especially w/ risk factors)
Urinalysis Hallmark	Muddy Brown Granular Casts, RTECs	WBC Casts, Eosinophiluria, Sterile Pyuria	Hematuria, Pyuria, Sloughed Papillae (rarely seen)
Key Lab/Diagnostic	FeNa >2%, Urine Osmolality <350 mOsm/kg	Peripheral Eosinophilia	Imaging (CT/IVP): Ring Shadow, Clubbed Calyces
Histology Buzzword	Proximal tubule damage, loss of brush border	Interstitial Infiltrate with Eosinophils, Tubulitis	Coagulative Necrosis of Papillae
Primary Treatment	Supportive, Remove Toxin, Fluids, Dialysis if severe	Stop Offending Agent, Corticosteroids may be used	Manage Underlying Cause, Supportive, Relieve Obstruction (if any)

Treatment

---